Effects of suprofen and other prostaglandin synthetase inhibitors in a new animal model for myometrial hyperactivity.
An in situ model for studying factors related to dysmenorrhea and for evaluating drugs for their inhibitory effects on uterine contractility induced by arachidonic acid and prostaglandins has been developed. Intravenous administration of arachidonic acid and PGF2 alpha to guinea pigs during the late stage of the estrous cycle, induced dose related uterine contractions and an elevation in uterine basal pressure similar to that seen in patients with dysmenorrhea. Pretreatment with prostaglandin synthetase inhibitors inhibited the response to arachidonic acid. The order of relative potency was suprofen (1) greater than indomethacin (0.65) greater than naproxen (0.52) greater than ibuprofen (0.43) greater than aspirin (0.31). The effectiveness or maximal response for suprofen was significantly greater than that of the other compounds tested. Simultaneous administration of suprofen with PGF2 alpha also blocked induction of uterine contractions, suggesting the possibility that suprofen also antagonizes PGF2 alpha receptor binding. Bradykinin also induced uterine contractions, an effect blocked by pretreatment with suprofen. Finally, histochemical studies demonstrated stimulation of uterine catecholamine levels (norepinephrine) by arachidonic acid, PGF2 alpha and bradykinin. These effects were blocked by suprofen. These data suggest that suprofen, an analgesic prostaglandin synthetase inhibitor, may be of use in the clinical treatment of uterine contractions associated with primary dysmenorrhea.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D015237:Dinoprost; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004412:Dysmenorrhea / Q000503:physiopathology; D005260:Female; D006168:Guinea Pigs; D006651:Histocytochemistry; D008856:Microscopy, Fluorescence; D010666:Phenylpropionates / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology; D013496:Suprofen / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000378:metabolism
D001095:Arachidonic Acids; D002395:Catecholamines; D016861:Cyclooxygenase Inhibitors; D010666:Phenylpropionates; D011460:Prostaglandins F; D016718:Arachidonic Acid; D013496:Suprofen; D015237:Dinoprost; D001920:Bradykinin